Our broad objective is to understand how various nutritional and hormonal factors govern the synthesis of fat in animals. We are particularly interested in the very rapid and large activation which we have observed almost immediately after mice ingest a fat-free, glucose-rich test-meal. The flux of glucose-C to fatty acids (microgram C/min) in mice before and shortly after they ingest various glucose-rich test-meals will be estimated in steady and non-steady states. Steady states in fed mice will be obtained by suppressing alimentary hyperglycemia (feeding 2 consecutive test-meals). (U-14C)glucose will either be injected intranvenously or added to the test meals. Serial measurements in individual mice of plasma glucose concentrations and specific activities, and measurement of total lipid fatty acid -14C in various tissues at one point in time are the data required for the flux estimates. Among the parameters to be studied are: (a) influence of noncarbohydrate nutrients, (b) rates of lipogenic activation and inactivation, (c) tissues in which lipogenic activation occurs, (d) magnitude of the changes, (e) effects of multiple meals and prior fasting, (f) re-evaluation of quantitative differences in lipogenic activation between nibblers and gorgers, (g) requirements for insulin (diabetic mice) and other hormones, and (h) relationship of lipogenic activation to carbohydrate-induced hypo- and hypertriglyceridemias. In later years, we shall investigate the molecular basis of rapid lipogenic activation. BIBLIOGRAPHIC REFERENCES: Palmquist, D. L., Learn, D. B., and Baker, N. Re-evaluation of effects of meal feeding on lipogenic activation by glucose in rats. J. Nutr., April, 1977, in press. Baker, N. Measurement of glucose and liver glycogen synthesis in mice using double labeled substrates. Fed. Proc., February, 1977, in press.